1. Field of the Invention
The present invention relates to a technology for analyzing a body fluid sample, and particularly relates to a handling method of a body fluid sample and an analysis apparatus using the handling method which can sample the body fluid samples using a plurality of pipetting devices.
2. Description of the Prior Arts
Analysis of body fluid samples such as blood and urine samples from patients is widely performed in order to diagnose pathologies, and automated analysis apparatuses are used in hospitals and clinical examination rooms.
In order to diagnose the pathologies, examination results obtainable by only one automatic analyzer are insufficient in most cases. In such a case, it is necessary to collect examination data from a plurality of analysis units. Japanese Patent Application Laid-Open Nos.9-281113 and 9-304396 disclose an analysis system which can analyze various kinds of analysis items by one system.
These prior arts propose an analysis system in which a plurality of analysis units for biochemical analysis are arranged along a sample rack transportation line, and a sample rack from a rack supply unit is dropped in at any one of the analysis units to pipette a sample on the sample rack using a pipette nozzle.
The U.S. Pat. No. 5,470,534 discloses an analysis system in which a biochemical analyzer, an immune analyzer and a nucleic acid analyzer are arranged along a transportation path for a sample bottle so that a single sample can be measured by each of the analyzers. In this prior art, whether or not the sample should proceed to a second measuring stage is determined depending on an analysis result in a first measuring stage. A biochemical analysis item is analyzed in the first measuring stage, and a sample necessary to proceed to the second measuring stage in order to identify a pathology is analyzed by the immune analyzer and/or the nucleic acid analyzer in the second stage.
On the other hand, in the apparatus automatically analyzing body fluid samples, many samples are successively pipetted usually using one pipette nozzle. Therefore, there arises a contamination problem of the following samples caused by residue of the preceding sample on the pipette nozzle. A technology in regard to carry-over of this kind is disclosed, for example, in Japanese Patent Application Laid-Open No.4-169851. In this example, analysis of a biochemical analysis item such as measurement of components usually contained in blood and analysis of an immune analysis item such as detecting an antigen or an antibody utilizing cohesive reaction of latex particles using a row of reaction containers formed in a circular shape.
Further, Japanese Patent Application Laid-Open No.4-169851 points out that useless consumption of washing solution can be prevented by spending sufficient washing time in washing a reagent pipette nozzle after pipetting a reagent for an immune analysis item using a washing solution or by increasing a delivery flow rate of the washing solution to wash the reagent pipette nozzle, and by spending short washing time in washing a reagent pipette nozzle after pipetting a reagent for a biochemical analysis item or by decreasing a delivery flow rate of the washing solution to wash the reagent pipette nozzle.
In addition, Japanese Patent Application Laid-Open No.4-169851 also points out that in a case of a sample pipette nozzle different from the reagent pipette nozzle, useless consumption of washing solution can be prevented by controlling the flow rate of the washing solution.
As an another type to pipette a body fluid sample, it is widely known to use a disposable nozzle tip. For example, U.S. Pat. No. 5,639,425 discloses a method comprising the steps of providing a tip holder at a position within a movable range of a coupling tube which can be coupled to a nozzle tip, transporting a nozzle tip from a tip rack on which many nozzle tips are arranged to the position of the tip holder, then coupling the nozzle tip with an end portion of the coupling tube on the tip holder, discharging a sample sucked inside the coupled nozzle tip into a reaction container, and after discharging the sample, removing the nozzle tip from the coupling tube at a tip detaching station.
Moreover, Japanese Patent Application Laid-Open No.225755 discloses an analysis apparatus in which a plurality of reaction parts are arranged near the transportation line for transporting the sample rack, and a bypass line and a sample dilution part are disposed between the transportation line and the respective reaction parts.
This reference discloses further that the plurality of reaction parts are constructed to analyze the sample by a calorimathod, an ion selective electrode method and an immunity method. In this example, the sample rack is moved from the transportation line to the bypass line by a rack changer provided in the transportation line, and a dilution arm pippetes the sample from the sample rack on the bypass line to the sample dilution part, and other pippetting arm having a different construction pippetes the sample from the sample dilution part to the reaction part. Furthermore, it is disclosed that it is preferable for the plurality of the reaction parts to be arranged in a sequence to prevent the mutual contamination between the samples.
3. Discussion of the Prior Arts
Many methods for measuring immune analysis items include an operation for binding a label substance to solid phase utilizing an antigen-antibody reaction (that is, an immune reaction).
In a case where there are needs to analyze both of an immune analysis item through such a method and a biochemical analysis item through a method of measuring an absorbance of a reaction solution produced as a result of the chemical reaction, or there are needs to analyze a DNA analysis item and biochemical analysis item, it is convenient for handling samples that plurality of analysis units are placed in an analysis system and a single sample bottle is commonly used for each of the analysis units.
However in U.S. Pat. No. 5,470,534 in connection with the analysis systems of such a type, there is no description on measures for avoiding the carry-over between samples.
Furthermore, in Japanese Patent Application Laid-Open No.9-281113 and Japanese Patent Application Laid-Open No.9-304396, plurality of analysis units are disclosed, however there is no description to arrange both of a biochemical analysis unit and a immune analysis unit, or to arrange both of the biochemical analysis unit and a DNA analysis unit.
Japanese Patent Application Laid-Open No.4-169851 proposes that the carry-over is avoided only by washing operation using a single pipette nozzle repetitively used for both of a biochemical analysis item and an immune analysis item. However, since there is a limitation in the actually applicable washing time or washing flow rate, it is difficult to eliminate the effect of carry-over on a measured value of an immune analysis item in which existence of an extremely small amount of a residual sample causes a problem.
According to the construction using the disposable nozzle tip described in U.S. Pat. No. 5,637,425, there is no problem on the effect of carry-over between samples since the nozzle tip is exchanged for each sample. However, since there are the coupling operation and the detaching operation of the nozzle tip for each sample, the method has a disadvantage in that a sufficient processing capacity can not be attained when a large volume of analysis items such as biochemical analysis items must be processed in a short time.
In a analysis apparatus described in Japanese Patent Application Laid-Open No.2-25755, there is not any difference between the construction of the plurality of the reaction parts, and it is intended to prevent the mutual contamination between the samples only by changing the arranging sequence of the reaction parts. However, the dilution arm and the pippeting arm are commonly used for all of the samples repeatedly, therefore, it becomes difficult to avoid the carry-over between the samples caused by using these arms.